PROGRESSION OF A VESICULAR STOMATITIS-VIRUS INFECTION IN PRIMARY LYMPHOCYTES IS RESTRICTED AT MULTIPLE LEVELS DURING B-CELL ACTIVATION

Small resting B cells do not support a productive vesicular stomatitis virus (VSV) infection, but are induced by B cell activators to become fully permissive for VSV replication. Nonpermissive B cell populations restrict VSV expression at multiple points: transcript levels, translation, and maturation. Unstimulated resting G(0) B cells can be infected by VSV and support the synthesis of all VSV mRNAs. Steady-state levels of viral transcripts are selectively enhanced by T cell-derived cytokines to an extent comparable with that seen for cytokine-regulated cellular mRNAs. However, viral proteins are not detected in immunoprecipitates from unstimulated or cytokine-stimulated B cells despite the fact that viral mRNAs are associated with polysomes and can be translated in vitro. This translational block is released by stimulation of infected B cells with mitogenic anti-Ig or LPS, or non-mitogenic PMA. VSV virion maturation is also regulated by activation signals, because neither anti-Ig- nor PMA-stimulated B cells produce high levels of infectious VSV particles. Because anti-Ig stimulation supports viral genome replication, maturational arrest is apparently at virus assembly or release. PMA and ionomycin induces changes beyond those seen with anti-Ig, because these B cells produce PFUs at levels comparable with those seen with LPS-activated B cells and VSV-permissive cell lines. Activation-dependent regulation of virus expression provides a new paradigm for assessing activator-induced events in B cell differentiation not revealed by previous assessments of proliferation or Ab synthesis.